Retrovirus-induced immunodeficiency in the mouse, MAIDS, is caused by a replication defective MuLV (BM5def) that expresses only an unusual Gag gene in contrast to the HIV lentivirus responsible for AIDS. MAIDS thus clearly differs from AIDS in pathogenesis, but may shed light on how retroviruses can disrupt the immune system and how retroviruses interact with cellular components. We have followed up on an unusual aspect of MAIDS, the production of wild type levels of IgE in the absence of IL-4, a cytokine previously thought to be an absolute requirement for production of IgE. We discovered that MAIDS develops normally in mice lacking STAT6, a normally important signaling molecule for IgE expression. In contrast, IgE expression is inhibited in mice deficient in one of the molecules that contributes to receptors for IL- 4 and IL-13. This suggests that IL-13, a cytokine recently found to contribute to asthma in humans is a driving force for IgE expression in MAIDS. In other efforts to understand IgE regulation, we studied mice with a mutation in the gene (ATM) that causes ataxia telangiectasia ? a disorder characterized by immunodeficiency and cancer susceptibility. We found that this mutation impairs IgE. The defect involving the mechanisms responsible for rejoining broken strands of DNA that develop as part of the process of switching to IgE from IgM production. We found that this block can be overcome by infection with the viruses that cause MAIDS.Previous studies demonstrated a role for the cytokine interferon (IFN)-gamma in MAIDS. To understand IFN signaling, we have been studying mice unable to signal through an IFN pathway involving a transcriptional repressor, ICSBP, because of a gene ?knockout?. These mice develop a disease that resembles chronic myelogenous leukemia (CML) in humans including a massive accumulation of neutrophils in blood. We found that in mice lacking ICSBP, there is a defect in programmed cell death in the myeloid/neutrophil cell lineage, demonstrating that ICSBP is a novel regulator of apoptosis. - IgE, IL- 4, STAT6, Fv1, KIF4